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环状ANKRD52 通过海绵吸附 miR-497-5p 并上调 BIRC5 表达促进肝癌的发生。

CircANKRD52 Promotes the Tumorigenesis of Hepatocellular Carcinoma by Sponging miR-497-5p and Upregulating BIRC5 Expression.

机构信息

Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China.

Department of Gastroenterology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

出版信息

Cell Transplant. 2021 Jan-Dec;30:9636897211008874. doi: 10.1177/09636897211008874.

Abstract

CircRNAs participate in the pathogenesis of a variety of cancers. Previous studies showed that baculoviral IAP repeat containing 5 (BIRC5) can promote tumor progression. But, the mechanisms by which circRNAs regulate BIRC5 expression in hepatocellular carcinoma (HCC) remain unknown. The clinical prognosis of BIRC5 or miR-497-5p expression in patients with HCC was assessed by TCGA RNA-seq dataset. hsa_circ_0026939 (circANKRD52) or BIRC5 was identified to bind with miR-497-5p by luciferase gene report, RIP and circRIP assays. MTT, colony formation, Transwell assays and a xenograft tumor model were used to estimate the role of miR-497-5p or circANKRD52 in HCC cells. As a result, we found that elevated expression of BIRC5 or decreased expression of miR-497-5p was linked to poor survival in HCC. Restored expression of miR-497-5p repressed cell proliferation, colony formation and invasiveness by targeting BIRC5, but its inhibitor showed the opposite results. Furthermore, circANKRD52 possessed a tumor-promoting effect by acting as a sponge of miR-497-5p and thereby upregulated BIRC5 in HCC cells. In conclusion, our findings demonstrated that circANKRD52 enhances the tumorigenesis of HCC by sponging miR-497-5p and upregulating BIRC5 expression.

摘要

circRNAs 参与多种癌症的发病机制。先前的研究表明杆状病毒 IAP 重复序列 5(BIRC5)可以促进肿瘤进展。但是,circRNAs 调节 HCC 中 BIRC5 表达的机制尚不清楚。通过 TCGA RNA-seq 数据集评估了 BIRC5 或 miR-497-5p 在 HCC 患者中的临床预后。通过荧光素酶基因报告、RIP 和 circRIP 测定鉴定 hsa_circ_0026939(circANKRD52)或 BIRC5 与 miR-497-5p 结合。MTT、集落形成、Transwell 测定和异种移植肿瘤模型用于评估 miR-497-5p 或 circANKRD52 在 HCC 细胞中的作用。结果发现,BIRC5 表达升高或 miR-497-5p 表达降低与 HCC 患者的不良生存相关。miR-497-5p 的恢复表达通过靶向 BIRC5 抑制细胞增殖、集落形成和侵袭性,但其抑制剂则表现出相反的结果。此外,circANKRD52 通过充当 miR-497-5p 的海绵并上调 HCC 细胞中的 BIRC5,发挥促肿瘤作用。总之,我们的研究结果表明,circANKRD52 通过海绵 miR-497-5p 和上调 BIRC5 表达增强 HCC 的肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9972/8058805/cae1cc1f6628/10.1177_09636897211008874-fig1.jpg

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